Table 2.

Requirements for successful transition of a new biomarker from the research environment to routine clinical practice

Requirement	Comment
An unmet clinical need which is clearly understood 33	The purpose of the test should be clear, its use evaluated within a care pathway and its effect on outcome compared directly with existing best practice in the population for which it is intended 35.
Appropriate and well-characterized clinical specimens for both discovery and qualification which mirror the relevant clinical population.	Numerous critical factors must be taken into account when collecting specimens for the studies of new biomarkers, whether for a specific clinical study or for a biobank, as has recently been comprehensively reviewed 14. It is highly desirable that the results of parameters such as albumin, creatinine and CRP should be available for banked specimens to enable interpretation of results and ensure appropriate matching of patient and control samples.
An appropriate and well-validated discovery platform which is robust, reliable and relatively simple to operate.	The importance of using internal standards, identifying measured components, developing standards for calibration and quality control, identifying peaks in spectra and applying established standards for method evaluation have previously been highlighted 36.
Clinical evidence for the biomarker of	Evidence of biomarker-disease association is necessary but not sufficient for effective clinical performance. The critical question is “Do patients undergoing the diagnostic test fare better than similar untested patients?” 37.
• Association with the relevant disease
• Assessment of clinical utility and impact
• Circumstances where use of the test would be unjustified
Rigorous early investigation of pre-analytical factors that might influence interpretation of test results, including the effect of	Quality requirements previously described in detail for tumour marker measurement using immunoassay, mass spectrometry and microarray techniques are relevant to all new tests 23.
• Specimen type, specimen timing and specimen handling
• Stability in transit and during long-term storage
• Freeze–thawing
• Intra-individual biological variation
• Relevant interventions (e.g. biopsy) or medication
Analytical evidence for the biomarker measurement of acceptable technical performance, including
• Linearity on dilution
• Accuracy
• Precision
• Reproducibility
A prototype assay method suitable for early evaluation	Early transfer of a validated biomarker from the research laboratory to a specialist referral laboratory enables confirmation of transferability and assessment in a clinical setting. Some tests may be most appropriately provided by specialist laboratories (as is current practice, e.g. for gut hormone screens) with possible later transfer to a high-throughput laboratory.
Transfer of the biomarker to a routine IVD platform, which is only likely if there is	This step represents much greater financial investment than development of the prototype method 33. Introduction of a new test onto an analytical platform may also require modification of existing tests with other implications (e.g. for product inserts, etc.).
• Convincing evidence of sufficient clinical utility to warrant broad commercial uptake
• High likelihood that regulatory approval will be granted
Introduction of the biomarker into the routine clinical laboratory requires	Commissioning diagnostic tests is more sophisticated than simply procurement or contracting procedures. The core of the commissioning process is identification of the clinical need that will be met by the use of the test and the contribution it will make to the patient pathway 20.
• Commissioning the new test because it demonstrably meets an identified clinical need